The objective of this project is to characterize humoral and cellular effector mechanisms of tissue injury in animal models of African trypanosomiasis. In infected rabbits we have characterized morphologic injury; measured glomerular and renal tubular function and assessed phlogistic properties of circulating immune complexes and polyclonal B cell activation. Necropsy of 34 infected rabbits sacrificed at 7-44 days revealed focal perivascular inflammation of the ears, eyes and testes. In lymphoid tissues there was marked hyperplasia of the spleen and lymph nodes combined with thymic atrophy. Deposits of IgG, IgM and C3 in renal glomeruli were associated with glomerular hypercellularity; the hypercellularity was due predominantly to the influx of monocytes. Functional studies of glomerular permeability in vitro showed no decrease in infected rabbits (or rats). Tubular function in rabbits showed an 80 percent depression at 3 and 4 weeks. Circulating immune complexes (IC) were detected in infected rabbits. These IC contained IgG and IgM but no trypanosomal antigens. The in vitro release of beta-glucuronidase, lysosyme and neutral proteinase from human neutrophils was measured; sera from infected rabbits led to enhanced enzyme secretion compared to control sera. Polyclonal B cell activation was measured by spontaneous production of serum antibodies to dinitrophenol and by splenic plaque-forming antibodies to sheep red blood cells. DNP antibodies increased 115% by day 14, and declined rapidly after treatment with an anti-trypanosomal drug (Berenil). Splenic plaque-forming cells followed a similar pattern.